The Orioles have won only 12 times this season, but three of those decisions have come in their last three games.
Cleveland's only hits off Guthrie (2-4) were an RBI single by Jhonny Peralta in the first and a leadoff single by Travis Hafner in the seventh. In between those hits, Guthrie retired 16 straight batters.
Baltimore backed up Guthrie with a 14-hit attack. Luke Scott, Ty Wigginton and Corey Patterson had three hits each and Miguel Tejada had a two-run single during a four-run sixth.
Justin Materson (0-4) was roughed up for six runs on eight hits in 5 1/3 to take the loss.
The game was delayed at the start for 67 minutes by rain.